This randomized phase II trial studies combination chemotherapy when given together with vismodegib to see how well it works compared with combination chemotherapy without vismodegib in treating patients with advanced stomach cancer or gastroesophageal junction cancer. Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Vismodegib may stop the growth of stomach or gastroesophageal junction cancer by blocking the growth of new blood vessels necessary for tumor growth. It is not yet known whether combination chemotherapy is more effective when given with or without vismodegib in treating stomach cancer and gastroesophageal junction cancer.

Median Progression-free Survival (PFS) [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]

PFS is defined as the time from randomization until objective tumor progression or death from any cause and is evaluated per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Secondary Outcome Measures:

Objective Response Rate [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]

Defined as the percentage of the patients who had complete response (CR) or partial response (PR) per RECIST 1.1.

Overall Survival [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]

Defined as time from randomization day until death from any cause.

Incidence of Toxicities (Grade 3 and Higher) [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]

Defined as percentage of patients who experienced a toxicity with grade 3 or higher related to the protocol therapy. Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0

Incidence of Toxicities (grades1 and 2) [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]

Defined as percentage of patients who experienced a toxicity with grade 1 or 2 (worst grade) related to the protocol therapy. Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.

Patients must have histologically or cytologically confirmed gastric or gastroesophageal junction (GEJ) adenocarcinoma not amenable to surgical resection

Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan

No prior chemotherapy for advanced disease; patients may have receive adjuvant chemotherapy or chemoradiation if > 6 months has elapsed since completion of treatment

Must be willing to provide blood and tissue samples for research purposes; patient has the right to later withdraw consent for research studies and/or tissue specimens

Patients must agree to placement of a central venous catheter for chemotherapy administration

Patients must be able to swallow whole capsules

Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin), must be on a stable, therapeutic dose and have close monitoring of their levels

Women of child-bearing potential and men must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry, for the duration of study participation, and for at least 12 months post-treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Pregnancy testing: women of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL) within 10-14 days and within 24 hours prior to the first dose of GDC-0449/placebo (serum or urine); a pregnancy test (serum or urine) will be administered every 4 weeks if their menstrual cycles are regular or every 2 weeks if their cycles are irregular while on study within the 24-hour period prior to the administration of GDC-0449/placebo; a positive urine test must be confirmed by a serum pregnancy test; prior to dispensing GDC-0449/placebo, the investigator must confirm and document the patient's use of two contraceptive methods, dates of negative pregnancy test, and confirm the patient's understanding of the teratogenic potential of GDC-0449/placebo

Female subjects of childbearing potential are defined as follows:

Patients with regular menses

Patients, after menarche with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding

Women who have had tubal ligation

Female subjects may be considered to NOT be of childbearing potential for the following reasons:

The patient has undergone hysterectomy and/or bilateral oophorectomy.

The patient is post-menopausal defined by amenorrhea for at least 1 year in a woman > 45 years old

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

Patients who have had chemotherapy or radiotherapy within 6 months prior to entering the study

Patients may not be receiving any other investigational agents

Patients with known brain metastases should be excluded from this clinical trial

History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449, 5-fluorouracil or oxaliplatin

Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption

Patients unable to swallow whole capsules

Patients with clinically active liver disease, including viral or other hepatitis or cirrhosis are ineligible

Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study

Pre-existing > grade 1 peripheral sensory neuropathy

Previous or concurrent malignancy; exceptions: treated basal cell or squamous cell skin cancer, in situ cervical cancer, or lobular carcinoma in situ in one breast; or other cancer which the patient has been disease-free ≥5 years

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00982592

Locations

United States, California

University of California at Davis Cancer Center

Sacramento, California, United States, 95817

United States, Illinois

University of Chicago

Chicago, Illinois, United States, 60637

Cancer Care Center of Decatur

Decatur, Illinois, United States, 62526

Decatur Memorial Hospital

Decatur, Illinois, United States, 62526

Crossroads Cancer Center

Effingham, Illinois, United States, 62401

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, United States, 60201

Ingalls Memorial Hospital

Harvey, Illinois, United States, 60426

Loyola University Medical Center

Maywood, Illinois, United States, 60153

Illinois CancerCare-Peoria

Peoria, Illinois, United States, 61615

Illinois Oncology Research Association CCOP

Peoria, Illinois, United States, 61615

Memorial Medical Center

Springfield, Illinois, United States, 62781-0001

United States, Indiana

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, United States, 46845

Indiana University Medical Center

Indianapolis, Indiana, United States, 46202

United States, Michigan

University of Michigan University Hospital

Ann Arbor, Michigan, United States, 48109

University of Michigan

Ann Arbor, Michigan, United States, 48109

United States, Missouri

Saint John's Mercy Medical Center

Saint Louis, Missouri, United States, 63141

United States, New York

New York Cancer Consortium

Bronx;, New York, United States, 10461

Albert Einstein College of Medicine

Bronx, New York, United States, 10461

Montefiore Medical Center - Moses Campus

Bronx, New York, United States, 10467-2490

Beth Israel Medical Center

New York, New York, United States, 10003

New York University Langone Medical Center

New York, New York, United States, 10016

Saint Luke's Roosevelt Hospital Center - Saint Luke's Division

New York, New York, United States, 10025

Columbia University Medical Center

New York, New York, United States, 10032

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10065

Weill Medical College of Cornell University

New York, New York, United States, 10065

United States, Ohio

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center